Résumé :
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Communication n° 495 Myoblast transplant therapy (MTT) can be envisioned as a clinical alternative in the treatment of several myopathies. The problems that remain to be solved to improve the efficiency of MTT is the massive early death of transplanted precursor cells and the limited proliferative capacity of these cells within the host's muscle. The impairment of post-transplanted cell survival is affected by a number of factors, including the host immune response. We recently showed that immunodeficient recipients mice such as RAG-/-?c-/-C5-/- and RAG-/-?c-/- are both attractive and efficient systems to support the in vivo development of human myoblasts as ascertained by the high levels of human muscle engraftment and donor tissue differentiation. However, even in these models, an important loss of cells is observed after myoblast transplantation. This prompted us to attempt strategies to analyze the human myogenic cell death in these mice, in order to understand these phenomena in a microenvironment in which the adaptative response was impaired. 5x105 human myoblasts were injected into the Tibialis Anterior (TA) muscles of RAG-/-?c-/- recipients. Mice were sacrificed after 0h, 1h, 3h, 6h, 24h, 3 days, 5 days and TA muscles were analyzed by immunofluorescence. Our preliminary results showed a high percentage of injected human myoblasts expressing molecules related to apoptosis (caspase3, TNFR and PARP) in the first hours after transplantation, with a decreased expression of these molecules in the transplanted cells after 24 hours. In addition, we observed a progressive arrival of MAC-1+ cells with a huge infiltration (located around the transplanted cells) 24 hours after myoblast transplantation. The knowledge of the mechanisms involved in the survival of transplanted human myoblasts, not related with the specific immune response of the recipient, will certainly be important to design new strategies for cell mediated therapy
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